In an effort to develop new, more effective forms of angioplasty, we have sought better understanding of the nature of focal coronary stenoses and their acute and chronic responses to intervention. Through the development of the clinical use of intravascular ultrasound (IVUS), we have shown that the composition and stiffness at focal chronic stenoses is remarkably different from adjacent angiographically normal vessel segments, whereas the total mass of atheroma is remarkably similar. The principal lesions currently treated by angioplasty have become rigid due to fibrosis and calcification, which prevent compensatory dilatation observed in more compliant (though heavily diseased) segments. Accordingly, successful interventions disrupt/alter the stiff constraining elements, thus irreversibly making them sufficiently compliant to permit vessel expansion. Successful therapy requires segmental (limited) rupture of the stiff annulus and creation of a large compliant arc. Acoustic transients created by rapid bubble expansion are the principal cause of this disruption in laser angioplasty. Directional atherectomy creates deep focal excisions that can make a small arc (approximately 60 degrees) highly compliant. Rotablators remove luminal calcification, thereby reducing wall stiffness. Following the expansion of "rigid" metallic stents at high pressures, the surrounding tissues generate significant compressive forces that cause an acute and chronic compressive narrowing of treated lesions. The narrowing of these lesions may be the major cause of restenosis.